Aluminum Amalgam Research Articles

Synthesis and Structures of Homoleptic Methyl- and Phenylthiomethylaluminium Complexes [Al(CH2SR)3](R = Me, Ph)

Sulfur-substituted methylmercury compounds [Hg(CH2SR)2](1a, R = Me; 1b, R = Ph) react with aluminium amalgam in refluxing toluene with transmetallation to give homoleptic tris(thiomethyl)aluminium complexes [Al(CH2SR)3](2a, R = Me; 2b, R = Ph) (degree of conversion: >80%, isolated yields: 2a 63%, 2b 41%). Their identities were confirmed by NMR spectros-copy (1H, 13C) and X-ray crystal structure analyses. In crystals of compound 2a the aluminium atoms possess a trigonal-bipyramidal arrangement with the coordination polyhedron defined by three carbon and two sulfur atoms. Two of the three CH2SMe ligands are bridging ligands (μ-η2; 1kC:2kS), the third one is terminal bound (η1; kC). The structure is polymeric. Crystals are threaded by helical chains built up of six-membered Al2C2S2 rings. Crystals of 2b are built up of centrosymmetrical dimers with six-membered Al2C2S2 rings having bridging CH2SPh ligands (μ-η2; 1kC:2kS). On each Al atom two terminal (η1; kC)CH2SPh ligands are bound. They exhibit quite different Al-C-S angles (116.7(4) and 106.5(3)?). Similar values (114.32115.7? and 109.52109.9?) were found in ab initio calculations of model compounds [{Al(CH2SR)3}2](3a, R=H; 3b, R=Me; 3c, R=CH=CH2). A conformational energy diagram for rotation of one of the terminal CH2SH ligand in the parent compound 3a around the Al-C bond is discussed in terms of repulsive interactions of lone electron pairs of sulfur atoms.

N4-(omega-Aminoalkyl)-1-[(omega-aminoalkyl)amino]-4- acridinecarboxamides: novel, potent, cytotoxic, and DNA-binding agents.

A series of DNA-binding potential antitumor agents, (omega-aminoalkyl)-4-acridinecarboxamides, has been prepared either by reduction of the corresponding (omega-aminoalkyl)-9-oxo-9, 10-dihydro-4-acridinecarboxamides with aluminum amalgam or by aminolysis of the corresponding (omega-aminoalkyl)-1-chloro-4-acridinecarboxamides with the suitable amine. The noncovalent DNA-binding properties of these compounds have been examined using a fluorometric technique. In vitro cytotoxic potencies of these derivatives toward six tumor cell lines, including human colon adenocarcinoma (HT29) and human ovarian carcinoma (A2780-sensitive, A2780cisR cisplatin-resistant, CH1-sensitive, CH1cisR cisplatin-resistant, and SKOV-3) cells, are described and compared to that of reference drugs. One highly DNA affinic analogue (3a) has been identified with a useful broad spectrum of cytotoxic activity in the 4-7 nM range (mean IC(50) of 6 nM).

ChemInform Abstract: 2-(Ethoxycarbonylmethyl)-1H-naphtho[1,8-de]-1,2,3-triazine Anion: A New Glycine Enolate Equivalent.

Abstract The titled triazine can be alkylated with LDA and a variety of alkyl halides: subsequent reduction with aluminium amalgam cleaves the naphthotriazine moiety to afford substituted α amino acids in excellent overall yields; the sequence defines a novel methodology that can be applied under non-acidic and largely non-aqueous conditions.

2-(Ethoxycarbonylmethyl)-1 H-naphtho[1,8- de]-1,2,3-triazine anion: a new glycine enolate equivalent

The titled triazine can be alkylated with LDA and a variety of alkyl halides: subsequent reduction with aluminium amalgam cleaves the naphthotriazine moiety to afford substituted α amino acids in excellent overall yields; the sequence defines a novel methodology that can be applied under non-acidic and largely non-aqueous conditions.

An Efficient Method to Construct the A,B-Rings Component toward Total Syntheses of Phycocyanobilin and Its Derivative as a Photoprobe

Abstract Total syntheses of phycocyanobilin and its derivative bearing a photoreactive group at the D-ring were accomplished by developing a new and efficient method for the construction of A,B-rings component, which consists of the Wittig-type new coupling reaction of 4-(1-methoxyethyl or 1-tosylethyl)-3-methyl-5-tosyl-1,5-dihydro-2H-pyrrol-2-one and a 2-formyl pyrrole derivative in the presence of nBu3P and a base, followed by reduction with aluminum amalgam and a subsequent acid or base treatment.

Synthesis and complexation of a novel soluble vic-dioxime with hydroxyethyl pendant arms

A new soluble vic-dioxime ligand namely 1,4-bis(2′-hydroxyethyl)-2,3-bis(hydroxyimino)-5,6-diphenylpiperazine, (LH2) containing optically active centers has been prepared as a mixture of isomers from (CNO)2 and N,N-bis(2-hydroxyethyl)stilbendiamine (1) which has been made by the reduction of the condensation of the product of benzaldehyde and 2-aminoethanol in the presence of aluminum amalgam. N,N-coordinated planar metal complexes of this ligand have been synthesized with NiII, CuII, CoII, PdII and UVIO2. Oxidation of (LH)2Co in the presence of a base, such as pyridine, leads to an octahedral complex (LH)2CopyCl containing pyridine and chloride as axial ligands in addition to vic-dioxime ligands. The structures of the ligand and its complexes are proposed on the basis of elemental analysis, 1H-n.m.r., mass, i.r. and u.v.–vis. spectral data.

Selective inhibitors of glial GABA uptake: synthesis, absolute stereochemistry, and pharmacology of the enantiomers of 3-hydroxy-4-amino-4,5,6,7-tetrahydro-1,2-benzisoxazole (exo-THPO) and analogues.

3-Methoxy-4,5,6,7-tetrahydro-1,2-benzisoxazol-4-one (20a), or the corresponding 3-ethoxy analogue (20b), and 3-chloro-4,5,6, 7-tetrahydro-1,2-benzisothiazol-4-one (51) were synthesized by regioselective chromic acid oxidation of the respective bicyclic tetrahydrobenzenes 19a,b and 50, and they were used as key intermediates for the syntheses of the target zwitterionic 3-isoxazolols 8-15 and 3-isothiazolols 16 and 17, respectively. These reaction sequences involved different reductive processes. Whereas (RS)-4-amino-3-hydroxy-4,5,6,7-tetrahydro-1,2-benzisoxazole (8, exo-THPO) was synthesized via aluminum amalgam reduction of oxime 22a or 22b, compounds 9, 11-13, and 15-17 were obtained via reductive aminations. Compound 10 was synthesized via N-ethylation of the N-Boc-protected primary amine 25. The enantiomers of 8 were obtained in high enantiomeric purities (ee >/= 99.1%) via the diastereomeric amides 32 and 33, synthesized from the primary amine 23b and (R)-alpha-methoxyphenylacetyl chloride and subsequent separation by preparative HPLC. The enantiomers of 9 were prepared analogously from the secondary amine 27. On the basis of X-ray crystallographic analyses, the configuration of oxime 22a was shown to be E and the absolute configurations of (-)-8 x HCl and (+)-9 x HBr were established to be R. The effects of the target compounds on GABA uptake mechanisms in vitro were measured using a rat brain synaptosomal preparation and primary cultures of mouse cortical neurons and glia cells (astrocytes). Whereas the classical GABA uptake inhibitor, (R)-nipecotic acid (2), nonselectively inhibits neuronal (IC(50) = 12 microM) and glial (IC(50) = 16 microM) GABA uptake and 4,5,6,7-tetrahydroisoxazolo¿4,5-cpyridin-3-ol (1, THPO) shows some selectivity for glial (IC(50) = 268 microM) versus neuronal (IC(50) = 530 microM) GABA uptake, exo-THPO (8) was shown to be more potent as an inhibitor of glial (IC(50) = 200 microM) rather than neuronal (IC(50) = 900 microM) GABA uptake. This selectivity was more pronounced for 9, which showed IC(50) values of 40 and 500 microM as an inhibitor of glial and neuronal GABA uptake, respectively. These effects of 8 and 9 proved to be enantioselective, (R)-(-)-8 and (R)-(+)-9 being the active inhibitors of both uptake systems. The selectivity of 9 as a glial GABA uptake inhibitor was largely lost by replacing the N-methyl group of 9 by an ethyl group, compound 10 being an almost equipotent inhibitor of glial (IC(50) = 280 microM) and neuronal (IC(50) = 400 microM) GABA uptake. The remaining target compounds, 11-17, were very weak or inactive as inhibitors of both uptake systems. Compounds 9-13 and 15 were shown to be essentially inactive against isoniazide-induced convulsions in mice after subcutaneous administration. The isomeric pivaloyloxymethyl derivatives of 9, compounds 43 and 44, were synthesized and tested as potential prodrugs in the isoniazide animal model. Both 43 (ED(50) = 150 micromol/kg) and 44 (ED(50) = 220 micromol/kg) showed anticonvulsant effects, and this effect of 43 was shown to reside in the (R)-(+)-enantiomer, 45 (ED(50) = 44 micromol/kg). Compound 9 also showed anticonvulsant activity when administered intracerebroventricularly (ED(50) = 59 nmol).

Reductive cleavage of NO bonds in hydroxylamines and hydroxamic acid derivatives using samarium diiodide

An efficient process for the reductive cleavage of NO bonds using samarium diiodide is detailed for a variety of structural types to define the scope and limitations of the method. The reduction is shown to be compatible with base sensitive substrates such as trifluoroacetamide derivatives, which cannot be reduced satisfactorily using aluminum amalgam or sodium amalgam. Direct quenching of the reduction mixture with acylating agents is demonstrated to provide high yields of protected amines in a one-pot process from the NO derivatives.

SYNTHESIS AND COMPLEXATION OF A NOVEL SOLUBLE VIC-DIOXIME

A new soluble vic-dioxime, l,4-bis(2-methoxyethyl-2, 3-bis(hydroxyimino)-5, 6-diphenylpiper-azine (LH2) has been synthesized as a mixture of isomers from dicyan di-N-oxide and 1, 2-diphe-nyl-l,2-bis(2′-methoxyethylamino)ethane, 1, which has been prepared through the reduction of the condensation product of benzaldehyde and 2-methoxyethylamine with the aluminium amalgam. LH2 gives N,N-coordinated planar metal complexes with CoII, NiII, CuII and PdII Oxidation of (LH)2Co in the presence of a base such as py or triphenylphoshine leads to octahedral complexes (LH)2Co(B)Cl. The uranyl complex of LH2 has a 1 :1 metal-ligand ratio and a binuclear structure with μ-hydroxo bridges.

Efficient Construction of A,B-Rings Component for Syntheses of Phycocyanobilin and Its Derivative

Abstract Total syntheses of phycocyanobilin and its photoactivatable derivative were accomplished by developing a new and versatile method for the construction of A,B-rings component, which consists of the Wittig-type new coupling reaction of 4-(1-methoxyethyl)-3-methyl-5-tosyl-1,5-dihydro-2H-pyrrol-2-one and a 2-formyl pyrrole derivative in the presence of nBu3P and a base, followed by reduction with aluminum amalgam and subsequent acid treatment.

Synthesis of bridgehead polycyclic 1,2‐diamines and 2‐amino alcohol derivatives as Rigid acetylcholine analogs

AbstractOxidation of dioxime 2a with NBS gave 3 and 4. A chair‐boat conformation has been established for 3 by X‐ray diffraction analysis, while 4 seems to exist in a chair‐chair conformation on the basis of NMR data. m‐Chloroperbenzoic acid oxidation of dioximes 2 gave polycyclic dinitro compounds 7. In some oxidations of 2a, nitroso dimer 8 was isolated, its structure being established by X‐ray diffraction analysis. Reduction of 7 with aluminium amalgam gave in good yields diamines 6, that were also obtained by reductive coupling from dioximes 2. Amino alcohols 14 were obtained by reductive coupling from monooximes 11. While 11a could be obtained in pure form from diketone 1a via 9a and 10a; hydrolysis of 10b to 11b failed. Azapolycyclic compounds 12 were obtained by hydrolysis of 10. Amino alcohol 14b was more appropriately prepared by reduction of nitro alcohol 15 obtained together with 7b by m‐chloroperbenzoic acid oxidation of a mixture containing monooxime 11b and dioxime 2b. From the oxidation of a mixture containing 11a, nitro ketone 16 was isolated in low yield. Amino alcohols 14 and diamines 6 were also characterized as cyclic carbamates 13 or ureas 5. Rigid analogs of acetylcholine 20 and 21 were obtained from 14 by standard procedures, compounds 17 and 18 being detected as intermediates. Neither muscarinic nor antiacetyl‐cholinesterase activity has been observed for compounds 20 and 21.

ChemInform Abstract: The Aluminum Amalgam Reduction of 2‐Nitroalkanols Promoted by Ultrasound.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Raw Materials for Alumina Ceramics

A brief presentation is made of the raw materials for alumina ceramics. The important source is the alumina trihydrate resulting from the Bayer process. Purification of the Bayer aluminate liquor to minimise organics, iron oxide and silica, reduction of sodium oxide content, special conditions of precipitation and calcination and fine grinding of the calcined material lead to the production of various grades of alumina. Other processes involve acidification of the aluminate liquor followed by drying and calcination or treatment of aluminium amalgam with water to precipitate aluminium hydroxide. Typical properties and applications of alumina ceramics are discussed. A survey of the world scene is made and the situation in India is briefly reviewed. The importance of introducing collaborative efforts to accelerate activities in this field in India is stressed.

The aluminum amalgam reduction of 2-nitroalkanols promoted by ultrasound

The sonochemical promoted aluminum amalgam reduction of 2-nitroalkanols provides an improved yield and accelerated conversion to the corresponding amino alcohols when compared to the nonultrasound (benchtop) reductions. The appearance of by-product hydroxylamines is minimized during the ultrasound promoted reaction. The product amino alcohols were conveniently acylated in situ with promotion by ultrasound thus affording the N-acyl derivatives in the same operation.

Alternative syntheses of bridgehead polycyclic 1,2-diamines and 2-aminoalcohols from di- and mono-oximes of some bicyclic diketones: Highly improved synthesis of tricyclo[3.3.1.0 3,7]nonane-3,7-diamine

Bridgehead polycyclic 1,2-diamines 4a and 4b have been obtained from dioximes 2a and 2b, respectively, by two alternative procedures: a) m-chloroperbenzoic acid oxidative coupling to 3a and 3b, followed by reduction with aluminum amalgam, and b) reductive coupling with aluminum amalgam. Similarly, the related 2-aminoalcohols 9a and 9b have been obtained from the corresponding monooximes 7a and 7b.

Ultrasound assisted oxidations and reductions in steroid synthesis

Ultrasonic irradiation made feasible some important oxidative and reductive reactions in steroid synthesis. These unusual conditions have improved existing methods and promoted new ones. The very common 5-en-3β-ol homoallylic system in steroids was oxidized to 4-ene-3,6-diones by a new one-step process, using tetra- n-propylammonium perruthenate with a co-oxidant, under sonochemical conditions. Ultrasonic irradiation has been also successfully used to promote the generation of radicals in the hypoiodite reaction, in order to prepare tetrahydrofurans as precursors of 19-hydroxy-Δ 5-steroids. Application of ultrasound to aluminium amalgam reductive opening of α,β-epoxy-ketones improved the reaction rates and yields of β-hydroxy ketones, in particular for α′-oxygenated counterparts. Zinc reduction of α,β-unsaturated oxosteroids has been also enhanced by ultrasound. Fast quantitative reactions led to olefins or allylic alcohols, according to the α-enone system used. Regio- and stereoselectivities are marked. A new Clemmensen-type reduction promoted on the last conditions gave a mild and effcient method to reduce selectively 3-oxo groups in polihydroxysteroids.

ChemInform Abstract: Sonochemical Reduction of α,β‐Epoxy Ketones and α′‐ Oxygenated Analogs by Aluminum Amalgam.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Sonochemical reduction of α, β-epoxy ketones and α′-oxygenated analogs by aluminium amalgam

The sonochemical reductive opening of α, β-epoxy ketones and their α′-oxygenated (-OH or -OAc) analogs by aluminium amalgam allows shorter reaction times, better yields of the respective β-hydroxy ketones and minimization of by-products. The rates of these reactions are affected by the intensity of the acoustic waves and by temperature.

Addition of a Reformatsky reagent to N-anthracene-9-sulfonyl and related imines: Synthesis of protected β-amino acids

The Reformatsky reagent tert-butoxycarbonylmethylzinc bromide adds in high yields to N-sulfonylimines, e.g. 1a–1d, derived by condensation of benzaldehyde dimethyl acetal with methanesulfonamide, toluene-4-sulfonamide, 4-(methoxycarbonyl)benzenesulfonamide and sulfamide: the products are protected β-amino acids 2a–2d. N-Deprotection occurs reductively (Na-naphthalene; low yields) for 2b and 2c or hydrolytically (refluxing aq. pyridine; 76% yield of amino acid 3a after acid hydrolysis of the t-butyl ester) for the sulfamide derivatives 2d. Anthracene-9-sulfonamide ( 6) is readily available by sulfonation and chlorination of anthracene, and condenses with aldehydes [RCHO; R = Ph, 4-FC 6H 4, 4-MeOC 6H 4, 4-NCC 6H 4, 2-furyl, ( E)-styryl], e.g. in the presence of TiCl 4/Et 3N, to yield imines 7a–7f, which after addition of tert-butoxycarbonylmethylzinc bromide give protected amino acids 8a–8f; however, 8f cyclizes to the sultam 9 via a spontaneous intramolecular Diels-Alder reaction. Reductive cleavage of the N-anthracene-9-sulfonyl group is much easier than for traditional N-sulfonyl protecting groups, as demonstrated by the deprotection of 8a and 8c using aluminium amalgam.

STUDIES ON ORGANOPHOSPHORUS COMPOUNDS LXXVI. A CONVENIENT SYNTHESIS OF 1-ALKYL-OR 1-ARYL-1-HYDROXY-2-N-HYDROXYLAMINOETHYLPHOSPHONIC ACIDS

Abstract A series of 1-alkyl-or 1-aryl-1-hydroxy-2-N-hydroxylaminoethylphosphonic acids was prepared by controlled reduction of dialkyl 1-alkyl-or 1-aryl-1-hydroxy-2-nitroethyl phosphonates with aluminum amalgam or stannous chloride followed by subsequent acid hydrolysis or dealkylation via the corresponding trimethylsilyl ester.